Molecular dynamics simulations of the conformational plasticity in the active pocket of salt-inducible kinase 2 (SIK2) multi-state binding with bosutinib.

ABSTRACT: The kinase domain is highly conserved among protein kinases 'in terms of both sequence and structure. Conformational rearrangements of the kinase domain are affected by the phosphorylation of residues and the binding of kinase inhibitors. Interestingly, the conformational rearrangement of the active pocket plays an important role in kinase activity and can be used to design novel kinase inhibitors. We characterized the conformational plasticity of the active pocket when bosutinib was bound to salt-inducible kinase 2 (SIK2) using homology modeling and molecular dynamics simulations. Ten different initial complex models were constructed using the Morph server, ranging from open to closed conformations of SIK2 binding with bosutinib. Our simulation showed that bosutinib binds SIK2 with up or

SUBMITTER: Shi M 

PROVIDER: S-EPMC9160496 | biostudies-literature | 2022

REPOSITORIES: biostudies-literature